In this proposal, we address two specific aims utilizing the infrastructure of the Arkansas Center for Birth Defects Research and Prevention, the Pediatric Cardiology Services at Arkansas Children's Hospital, and the National Birth Defects Prevention Study (NBDPS). The first specific aim is to determine the association between congenital heart defects (CHDs) and maternal passive and active smoking using maternal interview data from the NBDPS, the largest case-control study of congenital malformations ever conducted in the United States. The second specific aim will determine the association between CHDs and maternal passive and active smoking as measured in maternal hair nicotine. Objective measurement of maternal tobacco use and exposure during the critical period of cardiogenesis represents a unique application of hair biomarker analysis to the study of congenital heart defects. Hypothesis: Maternal tobacco use and exposure to tobacco smoke during pregnancy is associated with an increased risk of CHDs in infants. Among women who have infants affected by CHDs, self- reported exposure to tobacco smoke and hair nicotine levels will be higher than among women who have unaffected infants. Specific Aim 1: We will determine if women who have infants with CHDs are more likely to have used tobacco or been exposed to cigarette smoke (as determined by self-report) during their pregnancies than women whose infants do not have CHDs. Additionally, we will examine whether fetal tobacco exposure increases the risk of specific CHD subtypes. Specific Aim 2: We will determine if the risk of having an infant affected by a CHD increases with the amount of maternal tobacco use at the time of cardiogenesis as measured by postpartum maternal nicotine levels. We will also examine whether maternal variation in nicotine metabolism affects CHD risk by measuring aryl hydrocarbon receptor affinity. This study is unique in using hair nicotine as an objective measure to assess tobacco exposure and combining it with maternal self report to develop a risk profile for congenital heart defects that can be used as a tool in smoking cessation and other public health programs. In the US approximately 1 million infants are prenatally exposed to cigarette smoke during pregnancy each year. If a fraction of CHD cases could be prevented, it would translate not only to improved quality of life but millions of health care dollars saved. [unreadable] [unreadable] [unreadable]